The C. elegans P4-ATPase TAT-1 regulates lysosome biogenesis and endocytosis.
P-type adenosine triphosphatases (ATPases) of the Drs2p family (P4-ATPases) are multipass transmembrane proteins required to generate and maintain phospholipid asymmetry in membrane bilayers. In Saccharomyces cerevisiae, several members of this family control distinct transport events within the endosomal and secretory pathways. Comparatively, little is known about the functions of P4-ATPases in multicellular organisms. In this study, we analyzed the role of the Caenorhabditis elegans Drs2p homologue transbilayer amphipath transporter (TAT)-1 in intracellular trafficking. tat-1 is expressed in many tissues including the intestine, the epidermis and the nervous system. In intestinal cells, tat-1 loss-of-function mutants accumulate large vacuoles of mixed endolysosomal identity positive for the lysosomal protein LMP-1. In addition, they lack the same class of storage granules as lmp-1 mutants, suggesting that part of the tat-1 phenotype might result from LMP-1 sequestration in an aberrant compartment. Epidermal cells mutant for tat-1 contain acidified giant hybrid multivesicular bodies probably corresponding to endolysosomal intermediate compartments or deficient lysosomes. Finally, TAT-1 is required for yolk uptake in oocytes and an early step of fluid-phase endocytosis in the intestine. Hence, TAT-1 is required at multiple steps of the endolysosomal pathway, at least in part by ensuring proper trafficking of cell-specific effector proteins.
Ruaud
Anne-Françoise
AF
ENS, Biologie cellulaire de la synapse, INSERM U789, Paris, France.
Nilsson
Lars
L
Richard
Fabrice
F
Larsen
Morten Krog
MK
Bessereau
Jean-Louis
JL
Tuck
Simon
S
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology* / Q000648:ultrastructure; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics; D001678:Organelle Biogenesis; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D021381:Protein Transport; D013997:Time Factors; D014617:Vacuoles / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D049294:Phospholipid Transfer Proteins; D000251:Adenosine Triphosphatases; C522446:TAT-1 protein, C elegans